On February 10, 2014 Gilead announced that it had applied to the Food and Drug Administration (FDA) for the marketing approval of the combination of sofosbuvir (Sovaldi) and ledipasvir.

Watershed Moment
This is the first HCV combination therapy for genotype 1 that does not include interferon or ribavirin. The treatment period of 8 weeks for some is also shorter than prior therapies for HCV genotypes 1 a & b (12 to 48 weeks). Another big bonus is that the side effects are minimal especially when compared to the side effects of interferon and ribavirin.

One Pill, Once a Day
The new therapy consists of sofosbuvir, a polymerase inhibitor (400 mg), combined with ledipasvir, an NS5A inhibitor (90 mg)—formulated into one pill that is taken once-daily.

The treatment duration will be based on HCV health status—treatment naïve, treatment experienced, cirrhosis—for 8 or 12 weeks.

Gilead submitted the data from their ION studies that included about 2,000 HCV genotype 1 patients. The studies included people who had never been treated (treatment naïve), people who had not achieved a viral cure with a prior course of HCV therapy (including people who had previously been treated with HCV protease inhibitor combination therapy), and people with compensated cirrhosis.

The Ion Studies
The ION studies included about 2,000 patients who were treated with ledipasvir and sofosbuvir with and without ribavirin. The study included 1,512 treatment-naïve and 440 treatment-experienced patients. One hundred, thirty six of the treatment-naïve patients and 88 treatment-experienced patients had compensated cirrhosis. The SVR or cure rates are listed below for the 8 and 12 weeks groups that did not receive ribavirin.

Treatment naïve – 94% cure rate for 8 weeks of treatment

Treatment naïve – 95.4 to 97.7% cure rate for 12 weeks of treatment

Treatment experienced – 93.6% cure rate for 12 weeks of treatment

The drugs were awarded “breakthrough status” by the FDA which will help to speed up the FDA approval process. Gilead stated that the combination of drugs should be approved in 2014.

Good nutrition is a cornerstone of health, whether you have hepatitis C or not. We know that we “should eat better,” but what we eat and what we should eat don’t always match. Let’s face it, some of the less healthy foods are mouth-watering, and when confronted with a choice between pizza and tofu, pizza usually wins. As Mark Twain said, “The only way to keep your health is to eat what you don’t want, drink what you don’t like, and do what you’d rather not.”

Do you agree with Mark Twain? Do you look at diets and think that you would rather risk diabetes, heart disease, and stroke than give up your favorite food? Or, do you use denial, thinking about the taste rather than the consequences? What if you could have it both ways, the ability to eat good food and still be healthy?

There are many ways to achieve this goal. In this article I’ll focus on the concept of harm reduction, which simply means making less harmful choices. Harm reduction is usually applied to behaviors that have potentially serious consequences. Harm reduction began in the public health and drug policy arena when it was clear that the war on drugs was not solving any problems. Shame and punishment don’t help people change behaviors, whereas harm is reduced when drug users are empowered with choices. Providing street-based education and needle-exchange programs to users are examples of harm reduction. It works—not only is harm reduced, but drug users are more likely to get help for substance use.

What if we applied harm reduction concepts to eating? Dean Ornish, MD, Professor of Medicine at the University of California, San Francisco uses this approach. In the 1970’s, Ornish researched the effect of lifestyle choices on coronary artery disease. Decades later, he has amassed a body of research showing that diet, exercise, stress management, and support can reverse heart disease, type 2 diabetes, and lower cancer risk.

Ornish doesn’t preach—he gives choices—which is the essence of harm reduction. In his book, The Spectrum, he writes, “Foods are neither good nor bad, but some are more healthful for you than others. You have a spectrum of choices.” A dark chocolate fan, Ornish endorses occasional indulgence. “Studies have shown that the people who are most healthy overall are those who allow themselves occasional indulgences.”

Ornish categorizes foods into one of five groups—group 1 foods are the most healthful, group 3 are intermediate, group 5 are the least healthful. To maximize health, choose most of your foods from group 1 or 2, and minimize foods from groups 4 and 5. Ornish never uses the word “should.”

Before talking about specific foods, I need to say that diet plans vary widely. I am not endorsing a particular diet, and I am only using Ornish’s Spectrum because it illustrates the concept of harm reduction. The Ornish Spectrum is a mostly plant-based diet, and although meat-lovers can still eat meat on this program, they may prefer something more like the South Beach Diet. Both are liver-friendly. Pick the safe nutrition plan that works for you. As Ornish points out—diets based on deprivation and sacrifice are not sustainable; diets that include pleasure, feeling good, and freedom of choice are more likely to last.

Food-based Harm Reduction Strategies
Since few of us can follow a diet perfectly, here are strategies that will improve matters even if when you fall short of your goals. It’s like having your cake and eating it too, although you’d be better off having half a portion of cake, or eating an apple.

Eat smaller portions of less healthy foods.

For example: a large McDonald’s fries has 500 calories, 25 grams of fat, 3.5 grams saturated fat, 63 carbs, and 350 mg of sodium. Small fries cut that by more than half to: 230 calories, 11 grams of fat, 1.5 grams saturated fat, 29 carbs, and 160 mg of sodium. Kids' fries cut the small fries numbers by more than half.

Reserve the least healthy foods for special occasions.

A doughnut on your birthday is unlikely to kill you unless you choke on it. A doughnut every day is risky. If you aren’t ready to give up doughnuts, half a doughnut or one doughnut hole would be a better choice.

Be cautious about what constitutes a “special occasion.” Too many special occasions can sabotage the best intentions.

Make informed choices, not assumptions.

Sweet potato fries may sound healthier than regular fries, but may not be. At Carl’s Jr., a serving of sweet potato fries has more calories and fat than regular fries.

Keep a log of what you eat. Food and exercise journals are highly effective tools for change.

Journals don’t lie.

Some people will skip a food rather than log it.

If you aren’t meeting your goals, diaries can show you areas that might be changed or strengthened.

Reduce sodium intake. Go easy on processed foods, which are often high in sodium and other additives.

Don’t overdo it. A serving of nuts is healthy; a can of nuts is not.

The food you eat determines your health today and tomorrow. Food tastes good in the moment, but the effects can be devastating. To me, few indulgences are worth a lifetime of coronary artery diseases, fatty liver, diabetes, and so on. However, I am not ready for a life without one of the unhealthiest foods of all—movie popcorn. Even without extra butter it is packed with sodium, carbs and saturated fat. When I do indulge, I make it a small size and savor it. It is possible to eat well, enjoy life, and stay healthy.

The Patient Advocate Foundation announced that they received five million dollars in funding to provide financial assistance to people on medical treatment for hepatitis C (HCV). The Co-Pay Relief (CPR) program provides assistance for co-pay only for people who have insurance.

Co-pay coverage: $3,000 maximum per year

In order to be eligible for the co-pay program, the following criteria must be met:

Patient should be insured and insurance must cover the medication for which patient seeks assistance.

Social Security Disability and disability insurance companies will ask for your medical records when a claim is filed, and these records are the primary source used to determine if you meet their definition(s) of disability.

As part of the claims review process, Social Security, and frequently disability insurance companies, will also send you, the claimant, questionnaires once a claim has been filed. Some are for specific reasons or conditions such as pain, fatigue, or questionnaires concerning diabetes.

Most frequently, however, they will send a questionnaire asking about your ability to function generally. Although it may have a different name in some states or from some insurance companies, regardless of the title, it is designed to ask how your medical condition affects your daily life and your ability to function.

Although it is often debated by counselors how much they influence the disability decision, this is your opportunity to let the examiner go beyond the medical information and numbers and see just how your medical condition affects your daily life and the problems your symptoms cause you.

It is especially important to illustrate changes due to fatigue, pain, cognitive limitations, and other “subjective” symptoms. Whether they give much credence to the questionnaire or not, it is worth your while to complete it fully, if only for you to see how dramatically your life has changed. Be warned, however, it’s not usually a happy picture when you list all the changes your disease has caused over the years.

First, you need to plan what you are going to write, so it’s a good idea to make a photocopy of the questionnaire to make notes on, or to put trial answers on a blank sheet of paper before completing the actual questionnaire.

Next, review your symptoms. Make a list of them. Some people have been dealing with some symptoms for such a long time and have learned to accommodate them so well that they have forgotten about them as symptoms. Put your list somewhere it will be seen frequently, like the kitchen counter, in the TV room or bedside.

As you go through the next day or two you should recognize yourself doing tasks differently than you used to. Often this is due to a symptom you accommodated so well that you forgot about it. Do you take longer to groom? Did you change your hairstyle for convenience not looks? Do you short cut on meal preparation? Do you ration how often you go outside or upstairs or doing errands? Have your reading, TV or computer habits changed? Do you nap regularly? Note these shifts in habits on your sheet along with your symptoms. After two or three days, you will be ready to draft answers to the questionnaire.

Regardless of how the questions are worded, they want to know what adjustments you have had to make to accommodate your symptoms and what problems you still have even with some accommodation.

Some general rules to follow are:

Print or otherwise make sure you write legibly. No points are given for neatness, so don’t worry about strikeovers or cross-outs, but make sure what you write is readable.

Consider using a computer. It will be much easier to read. Be sure to include every question, preferably typed in bold to distinguish it from your answer.

NOTE: Sometimes, when you use a computer, your completed questionnaire looks “too good for a disabled person to complete.” However, you know how many hours and how many separate sittings you spent getting it to look like it does. If the questionnaire looks “too good” upon completion, note at the end of the questionnaire just how much time you spent completing it as well as any symptoms exacerbated by it. If someone assisted by writing, typing, or reviewing, acknowledge that as well.

Don’t leave any blanks. If there is nothing to say, write “N/A” or “None” to let them know you didn’t overlook the question.

Avoid one-word answers even if you are only asked to check “yes” or “no.” Expand on why you answered as you did, and, when possible, give an example or anecdote that illustrates your reply.

Don’t be intimidated by small space for answers. If you require more space, simply note “See Attached Sheet,” and put the answer on a blank sheet of paper. Make sure you put your name and Social Security or Claim number on every sheet, and number the answer to match the question.

The questions on a Daily Activities Questionnaire may vary slightly, but they generally cover the same areas in various degrees of detail:

What are your living arrangements? Do you live alone? Is there someone to help with the chores? Do you live in a house or apartment? Give appropriate details. For example, if you live in a two-story dwelling, comment on how you limit your trips up and/or down stairs due to pain/fatigue/etc., and on any accommodations you made in your living arrangements.

Describe what you do on an average day. Start with what time you get up and why you get up at that time. How long does it take to groom yourself? What do you have for breakfast and who prepares it, or is it just cold cereal or something else easy? How do you typically spend your morning—resting, running errands, going to the doctor?

What do you have for lunch? What do you usually eat? What shortcuts are taken in preparing lunch?

How do you spend the afternoon? Do you read, watch TV, nap, do some housework? If so, for how long?

What about dinner? Who fixes it? What is it, if you prepare it? How is this different from when you were healthy? Again, note all shortcuts that you use in meal preparation and clean up. What time do you go to bed? How well do you sleep?

Do you need help completing your housekeeping tasks? Here you can explain who helps or does the housekeeping, cleaning, laundry, yard work, and meal preparation. If you do these yourself, be sure to explain how you have adjusted to accommodate these tasks to your condition, i.e., whether you do them more slowly or not as often or in brief periods.

Again, as you answer this question, indicate how your health condition has affected your ability to complete your chores. For example, “I used to be able to change the sheets on the bed, but now I get so dizzy when I bend over that my husband (or friends) do it and the sheets only get changed twice a month now.”

Personal Care. This gives you the opportunity to tell how your grooming habits have changed, that it takes longer to complete, or that you don’t groom as carefully or as often as before. What special adjustments have you made due to your condition? One client who had memory problems said: “I keep all my grooming needs in a basket and take them out as I use them so I will know when I have done everything.”

Hobbies and interests. Reading and TV viewing habits. It is more important in this section to contrast your current interests and habits with those when you were healthy. Depending on the symptoms, many people are no longer able to engage in many of the physical activities they enjoyed when they were healthy. They also often find that because of fatigue or loss of cognitive ability, they don’t read novels or watch heavy dramas but favor lighter and shorter fare. It’s OK to say you go to the gym, especially if your doctor recommended it and your workout is lighter than it used to be.

Errands and transportation. They usually will ask about your driving ability or how you get around. They will also ask about shopping, who does it or, if you do, how often. Again, it is important to note any changes in your routine that you have made to accommodate your symptoms. Do you limit your driving to the neighborhood and daytime only? Do you buy smaller amounts so they are easier to carry or does a friend or spouse help with the major shopping trips?

Sometimes, you will have issues that aren’t directly addressed in the questions, but they show ways that your disability has affected you and your life. If there is no “Remarks” question at the end, add a sheet labeled, “Additional Information.”

If your condition has changed your level of patience or the way in which you deal with your family or with others, be sure to note that. If you have gone from being socially active to a more reclusive lifestyle, tell them about that as well.

When possible, give an anecdote that illustrates the change you are describing. For example: Name the TV show you turned off because it was too complicated to follow; tell about the stool or small table you placed just outside your door to set items on while unlocking the door; describe what tools and assists you purchased or created to make certain tasks easier on you; describe how you leave some groceries in the car and take them in at a later time.

This is the only opportunity you have to show how the medical condition has affected your life and your ability to function, so be sure to give all details of your changes, limitations and accommodations. It is important to explain it in detail. Do not assume that the analyst will assume anything; explain it thoroughly. In addition to showing how you are unable to work because of your condition, it will also give the analyst a more vivid picture of the human being that is suffering—something that can’t be learned from reading the medical facts.

Since the discovery of the hepatitis C virus (HCV) in 1989, risk of type 2 diabetes has been linked to HCV infection. HCV and diabetes are common conditions in the U.S., and researchers studied the relationship between the two, using recent data from the U.S. National Health and Nutrition Examination Survey from 15,128 adults.

The Bottom Line: HCV was not associated with diabetes or insulin resistance. Since elevated liver enzymes are linked to type 2 diabetes, these researchers suggest this as a possible explanation for previously reported connections between diabetes and HCV.

Editorial Comment: It is disconcerting to learn that a closely held piece of knowledge is not true. Medical professionals are human, and thus just as likely to find change difficult. It may take more research and time before this long-held “fact” is laid to rest.

The purpose of this Norwegian study was to evaluate liver fibrosis levels of deceased HCV+ injection drug users (IDUs). Using stored blood samples from IDUs who were treated for chemical dependency from 1970–1984, 220 deceased subjects were identified. Liver tissue was available from the autopsies of 102 subjects, of which 61 were HCV RNA+. Researchers used a 0 to 4-fibrosis scale, with 4 being cirrhosis.

16.4% of HCV RNA+ subjects had stage 3 fibrosis or cirrhosis compared to 2.4% of subjects who were positive for HCV-antibody but negative for HCV RNA. Of 18 HCV RNA+ subjects autopsied less than 15years after HCV exposure, none had fibrosis stage 3 or 4. Those exposed to HCV more than 25 years had a 35% risk of stage 3–4. The main cause of death was drug-related; death from liver disease occurred in less than 5%.

The Bottom Line: One in three Norwegian IDUs with chronic HCV developed stage 3 fibrosis or cirrhosis 25years or more after exposure.

Editorial Comment: Although I am grateful for the information gained by this study, participants did not give direct consent. I wonder if consent would have been more rigorously obtained if the subjects were not IDUs.

Low platelets (thrombocytopenia) are a common occurrence in HCV patients who have advanced fibrosis or cirrhosis. Since pegylated interferon-alfa (PEG) causes platelets to drop, PEG and ribavirin (RBV) therapy may be limited, delayed, or not initiated. Eltrombopag is a drug used to stimulate platelet growth, and this phase 3 study compared eltrombopag to placebo in its effect on sustained virologic response (SVR) 24 weeks after completion of PEG/RBV treatment.

Editorial Comment: Aviva Leber and Jordan J. Feld of the University of Toronto wrote an editorial questioning this study’s findings, highlighting the risks of eltrombopag (thromboembolic events, such as stroke). Leber and Feld advise that eltrombopag be used only when the benefits outweigh the risks, and to start the drug at the lowest dose.

This two-part study examined medical records of all infants born to mothers with HCV from 1993—2005. Despite recommendations from the American Academy of Pediatrics to test all HCV-exposed infants at 18 months or older for HCV antibody, the majority were not tested. The second part of the study examined the medical records of infants born to mothers with HCV after the implementation of electronic medical records from 2006—2011. Of the 67,112 infants born during the study period at this Cleveland, Ohio hospital, 280 had maternal HCV infection.

The Bottom Line: The use of electronic medical records resulted in a significant improvement of appropriate HCV testing among HCV exposed infants from 8% to 50%.

Editorial Comment: It is interesting that such a simple use of technology can yield such significant results.

HCV Drug Development News—Alan Franciscus, Editor-in-Chief

Once again it has been a very busy month in HCV drug development news. In addition to the news that Sovaldi/ledipasvir combination had been submitted to the Food and Drug Administration for marketing approval (see first article), there was also important news about AbbVie’s final results from their 6 phase 3 clinical studies and results from two phase 2 clinical studies by BMS and Gilead published in medical journals.

Abbvie
AbbVie announced on January 31, 2014 that it had completed (with results) the phase 3 studies of their combination of HCV inhibitors with and without ribavirin to treat HCV genotypes 1a & b in persons who were treatment naïve, treatment experienced and those with compensated cirrhosis. The majority of the 2,300 patients in the six studies were treated for 12 weeks.

AbbVie Inhibitors

Once-a-day: ABT-450 that is boosted with ritonavir and co-formulated with ABT-267 and dosed once-a-day;

The most common side effects were fatigue and headache. There were no treatment discontinuations in the ribavirin-free groups compared to 2% in the ribavirin groups.

Based on the similar cure rates between the groups that received ribavirin and the groups that did not receive ribavirin I think it is a good bet that AbbVie will apply to the FDA for marketing approval of AbbVie combination therapy that is interferon-free and ribavirin-free. The press release noted that AbbVie expects to launch their therapy in 2014.

This was an interferon-free and ribavirin-free study. The cure rates were similar between the groups that received 12 or 24 weeks of treatment, genotype 1a and 1b as well as CC and non-CC genotypes. The most common side effects were headache, asthenia (loss of or lack of strength) and gastrointestinal symptoms. There were no serious adverse effects (serious side effects) or treatment discontinuations.

The cure rate for patients who were treated for 12 weeks was 48% compared to 63% inthe group that was treated for 24 weeks. In the groups that achieved a rapid virological response (HCV RNA undetectable at week 4 of treatment) the cure rate was 68% in the 12-week treatment group compared to 81% in the 24-week treatment group.

These results are well below the cure rates for the Gilead clinical trials for sofosbuvir plus ledipasvir and further drug development for the 4-drug combination is unlikely.

HCV, Sleep and Quality of Life
It will not come as a shock to people living with hepatitis C that having hepatitis C reduces many aspects of quality of life including sleep. But many of the reduced quality of life issues have not been well documented. A recently released study from Hannover Medical School in Germany reported that women with HCV—without cirrhosis or hepatic encephalopathy—suffered from sleep disturbances. The study had a comparator arm of 19 age-matched women without HCV. What was interesting about this small study of women with HCV was that the same sleep disturbances were observed in 12 women who had HCV RNA (viral load) and those who were antibody positive, but viral load negative (8 women).

Sleep disturbances can lead to many problems and disorders such as insomnia, fatigue, depression and cognitive impairment.

Concrete conclusions can’t be drawn from this small study, but it is interesting and adds to the evidence that HCV is not just a liver disease, but can affect almost any part of the body including sleep. But in order to completely validate this conclusion more clinical trials are needed that have a large population of people with hepatitis C and that will compare the outcomes with a large population of people without HCV.

New HCV Recommendations
The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) in collaboration with the International Antiviral Society (IAS-USA) released “Recommendations for Testing, Managing, and Treating Hepatitis C.” As it states in the title the recommendations are for the whole spectrum of HCV, but the most striking feature is its recommendations for treatment. It is no surprise that the recommendations for genotype 1 treatment-naïve and treatment-experienced patients who can receive interferon was sofosbuvir, ribavirin and pegylated interferon for 12 weeks or alternately simeprevir, ribavirin and pegylated interferon for 24 weeks (with some caveats).

What was surprising was the recommendation to treat with sofosbuvir plus simeprevir with or without ribavirin for those who are not eligible for interferon. They based their decision on the COSMOS clinical trial that reported very high cure rates in people who typically have sub-optimal cure rates.

The recommendations were based on clinical data and there is very much a lean towards the best possible treatment outcomes regardless of what has been approved by the FDA. The recommendations can be found at:www.hcvguidelines.org/